Grain splitting is a mechanism for grain coarsening in colloidal polycrystals.

In established theories of grain coarsening, grains disappear either by shrinking or by rotating as a rigid object to coalesce with an adjacent grain. Here we report a third mechanism for grain coarsening, in which a grain splits apart into two regions that rotate in opposite directions to match two adjacent grains' orientations. We experimentally observe both conventional grain rotation and grain splitting in two-dimensional colloidal polycrystals. We find that grain splitting occurs via independently rotating "granules" whose shapes are determined by the underlying triangular lattices of the two merging crystal grains. These granules are so small that existing continuum theories of grain boundary energy are inapplicable, so we introduce a hard sphere model for the free energy of a colloidal polycrystal. We find that, during splitting, the system overcomes a free energy barrier before ultimately reaching a lower free energy when splitting is complete. Using simulated splitting events and a simple scaling prediction, we find that the barrier to grain splitting decreases as grain size decreases. Consequently, grain splitting is likely to play an important role in polycrystals with small grains. This discovery suggests that mesoscale models of grain coarsening may offer better predictions in the nanocrystalline regime by including grain splitting.

Use of Virtual Reality for Pediatric Cardiac Critical Care Simulation.

Simulation is a key component of training in the pediatric cardiac intensive care unit (CICU), a complex environment that lends itself to virtual reality (VR)-based simulations. However, VR has not been previously described for this purpose. Two simulations were developed to test the use of VR in simulating pediatric CICU clinical scenarios, one simulating junctional ectopic tachycardia and low cardiac output syndrome, and the other simulating acute respiratory failure in a patient with suspected coronavirus disease 2019. Six attending pediatric cardiac critical care physicians were recruited to participate in the simulations as a pilot test of VR's feasibility for educational and practice improvement efforts in this highly specialized clinical environment. All participants successfully navigated the VR environment and met the critical endpoints of the two clinical scenarios. Qualitative feedback was overall positive with some specific critiques regarding limited realism in some mechanical aspects of the simulation. This is the first described use of VR in pediatric cardiac critical care simulation.

Local Melting Attracts Grain Boundaries in Colloidal Polycrystals.

We find that laser-induced local melting attracts and deforms grain boundaries in 2D colloidal crystals. When a melted region in contact with the edge of a crystal grain recrystallizes, it deforms the grain boundary-this attraction is driven by the multiplicity of deformed grain boundary configurations. Furthermore, the attraction provides a method to fabricate artificial colloidal crystal grains of arbitrary shape, enabling new experimental studies of grain boundary dynamics and ultimately hinting at a novel approach for fabricating materials with designer microstructures.

Oxygen and the copper chaperone CCS regulate posttranslational activation of Cu,Zn superoxide dismutase.

Oxidative stress leads to the up-regulation of many antioxidant enzymes including Cu,Zn superoxide dismutase (SOD1) via transcriptional mechanisms; however, few examples of posttranslational regulation are known. The copper chaperone for SOD1 (CCS) is involved in physiological SOD1 activation, and its primary function is thought to be delivery of copper to the enzyme. Data presented here are consistent with a previously uncharacterized function for CCS in the SOD1 pathway, namely mediating enzyme activation in response to increases in oxygen tension. Activity assays with pure proteins and cell extracts reveal that O(2) (or superoxide) is required for activation of SOD1 by CCS. Dose-response studies with a translational blocking agent demonstrate that the cellular oxidative response to O(2) is multitiered: existing apo-pools of SOD1 are activated by CCS in the early response, followed by increasing expression of SOD1 protein with persistent oxidative stress. This CCS function provides oxidant-responsive posttranslational regulation of SOD1 activity and may be relevant to a wide array of physiological stresses that involve a sudden elevation of oxygen availability.

Detection of a [3Fe-4S] cluster intermediate of cytosolic aconitase in yeast expressing iron regulatory protein 1. Insights into the mechanism of Fe-S cluster cycling.

Interconversion of iron regulatory protein 1 (IRP1) with cytosolic aconitase (c-aconitase) occurs via assembly/disassembly of a [4Fe-4S] cluster. Recent evidence implicates oxidants in cluster disassembly. We investigated H(2)O(2)-initiated Fe-S cluster disassembly in c-aconitase expressed in Saccharomyces cerevisiae. A signal for [3Fe-4S] c-aconitase was detected by whole-cell EPR of aerobically grown, aco1 yeast expressing wild-type IRP1 or a S138A-IRP1 mutant (IRP1(S138A)), providing the first direct evidence of a 3Fe intermediate in vivo. Exposure of yeast to H(2)O(2) increased this 3Fe c-aconitase signal up to 5-fold, coincident with inhibition of c-aconitase activity. Untreated yeast expressing IRP1(S138D) or IRP1(S138E), which mimic phosphorylated IRP1, failed to give a 3Fe signal. H(2)O(2) produced a weak 3Fe signal in yeast expressing IRP1(S138D). Yeast expressing IRP1(S138D) or IRP1(S138E) were the most sensitive to inhibition of aconitase-dependent growth by H(2)O(2) and were more responsive to changes in media iron status. Ferricyanide oxidation of anaerobically reconstituted c-aconitase yielded a strong 3Fe EPR signal with wild-type and S138A c-aconitases. Only a weak 3Fe signal was obtained with S138D c-aconitase, and no signal was obtained with S138E c-aconitase. This, paired with loss of c-aconitase activity, strongly argues that the Fe-S clusters of these phosphomimetic c-aconitase mutants undergo more complete disassembly upon oxidation. Our results demonstrate that 3Fe c-aconitase is an intermediate in H(2)O(2)-initiated Fe-S cluster disassembly in vivo and suggest that cluster assembly/disassembly in IRP1 is a dynamic process in aerobically growing yeast. Further, our results support the view that phosphorylation of IRP1 can modulate its response to iron through effects on Fe-S cluster stability and turnover.